Elastic connective tissue – ligamentum nuchae and fava
Instead of lots of collagen fibers, you have lots of elastin fibers
A type of regular connective tissue
Reticular tissue – lymphatic tissue and bone marrow
Can be classified as loose connective tissue
Adipose tissue – subcutaneous and omentum
Special Connective Tissue
Cartilage – trachea, pina, nose, joint cartilage
Bone -- skeleton
Blood – cardiovascular and hemopoietic tissue
Functions of Connective Tissue
Mechanical support
Structural support of organs
e.g. connective tissue surrounding gland to support gland
Connective tissue of any organ is called stroma and supports the parenchyma
Parenchyma is the functional part of an organ supported by the stroma
Packing material
“Mother nature’s mortar”
Fills in all that’s between
Rigid structural support
Mechanical Protection
Bony and cushioning
e.g. thoracic cage, skull, heel of foot
Energy storage and temperature regulation
Fat – stored energy and insulator
Metabolic support
e.g. blood vessel must go through stroma to get to parenchyma
stroma determine transportability of molecules and waste to parenchyma
Transportation of material
Protection against infection
e.g. immune system does most of its work in connective tissue
Inflammation is in connective tissue
Repair after injury
Composition of All Connective Tissues
Cells
Fixed
Responsible for synthesis and maintenance of extracellular matrix and particular connective tissue
Secretory cells secreting extracellular matrix and ground substances
e.g. fibrocytes, mesenchymal cells, reticular cells, adipocytes, osteocytes, and chondrocytes
Wandering
Transient cells that migrate in and out of extracellular matrix of connective tissue
e.g. macrophages, mast cells, plasma cells, leukocytes
Associated
Cells associated with blood vessels that are always within connective tissue
e.g. endothelial cells, smooth muscle cells, and pericytes
Relatively acellular with lots of extracellular space between cells filled by extracellular matrix
Extracellular matrix includes extracellular fibers and amorphous ground substances
Extracellular Fibers
Collagen fibers for strength
Reticular fibers for delicate support
Elastic fibers for stretch and flexibility
Amorphous Ground Substances
Interstitial fluid (water)
Proteoglycans
Complex macromolecules consisting of core protein with glycoaminoglycans (GAG) attached to it
Glycoproteins
Fixed Cells
Fibrocytes
Most common connective tissue proper
Vesicular nucleus with nucleolus – hard to identify cytoplasm
Probably mostly euchromatin visible on nucleus
Secretory cell
Fibroblast – “-blast” is still capable of division and capable of adding new matrix around it
Fibrocyte – “-cyte” terminally differentiated, incapable of dividing, and maintain existing matrix but can’t add new matrix
Can’t tell fibroblast from fibrocyte unless the fibroblast is dividing
Mesenchymal Cell
Looks and does the same thing as a fibroblast
Identify mesenchymal or fibrocyte by location
Only difference is that its location is pluripotential
Can differentiate to muscle, bone, cartilage, etc.
Reticular cells
Similar morphology to fibrocyte
Can identify reticular fibers around them
Secretory
Glycoproteins
Forms cell-covered fiber framework
White adipocytes
Diagnostic characteristic – lipid droplet is all one lipid droplet (unilocular)
Large cells with signet ring appearance with nucleus pushed to one side
Adipose tissue is called subcutaneous fascia
Function – lipid storage
Hypercellular obesity – increased number of fat cells
Worse type to have and thought to be caused by overfeeding during the first year of life
Hardest one to treat
Hypertrophic obesity – increased size of fat cells
Most common condition
Lipid Storage
Lipoprotein Lipase
Put fatty acids into adipose cell
Hormone Sensitive Lipase
Breakdown triglycerides to glycerol and fatty acids
Takes fatty acids out of adipose cell
Leptin
Protein produced by adipocyte
Targets hypothalamus to decrease food intake and increase energy consumption
Insulin
Stimulates insulin receptors on fat cells to synthesize and store lipids
Epinepherine and norepinepherine
Stimulate fat cells to break down lipids and release glycerol and free fatty acids
Brown fat cells
Smaller than white fat cell
Multilocular – several small lipid lakes in cytoplasm
Numerous mitochondria on EM level
Function is to produce heat
Free fatty acid uncouples oxidation process from ATP production
Thermogenin on mitochondrial membrane protein that permits back flow of H+ protons instead of using for ATP formation
“Parasite Eve”
Found in newborns that is thought to gradually be converted to white fat in the first year
Newborn mediastinum, aorta, axilla between scapula
Also found in hibernating animals
Wandering cells
Marcophage
“Big Eater”
Antigen presenting cell
Have lots of phagosomes, lysosomes, and phagolysosomes
Mono-nuclear phagocyte system
Derived from granulocytic-monocyte stem cell
Transported as monocytes in blood stream
When a monocyte leaves the blood and enters connective cell, it becomes a macrophages
Name dependent on location where monocyte leaves blood stream
Identify with vital dye ingestion such as Indian ink, trypan blue, carbon black
Can’t see cytoplasm
Foreign-body giant cell – in an inflammation situation, several macrophages fuse to surround and encapsulate foreign-body
Mast Cell
Full of granules
contain mediators of inflammatory response such as histamine, heparin, neutral protease, leukotrienes (C4 and D4), Eosinophilic chemotaxtic factor, neutrophilic chemotaxtic factor
Associated with small blood vessels
Antibody attaches to IgE receptor which interacts with antigen
Secondary signal via cAMP and phosophylation is activated that leads to activation of phospholipases and Ca2+ release which triggers release of granules
Important because of anaphylactic shock
Fluid leaking out of blood and entering connective tissue
Resulting swelling and dilation of blood vessels on a large scale
Blood pressure drops and patient goes into anaphylactic shock
Histamine also constricts smooth muscle in bronchia
Also releases cytokines such as TNFγ
Paracrine secretion – localized secretion that isn’t distributed throughout the body
Plasma cells
Morphologically eccentrically located nucleus (nucleus not in center)
Has cart wheel appearance
Packed with rough ER (visible on EM level)
Produces immunoglobulins (antibodies) and needs lots of rough ER
Terminally differentiated from B-lymphocytes
If shows up on a blood smear, patient has a massive infection somewhere
Extracellular Fibers
Collagen Fibers
Strength
Most common protein of the body
Lots of collagen fiber diseases
20% of all proteins
30% of dry weight of body
High tensile strength, inelastic yet flexible
Use as model of fiber organization and formation
Collagen can be organized into fibrils which are organized into fibers
Fibers are organized into bundles or fascicle
Fibers are barely visible on light microscope
Fibrils are made of trophocollagen molecules which are made of alpha chains
Each alpha chain is 1,000 amino acids containing lots of glycine, hydroxyproline, and hydroxylysine
Glycine is used as a diagnostic test for collagen wasting diseases
H+ bonding between hydroxyproline holds alpha chains together
Covalent bonds between lydroxylysine of adjacent tropocollagen molecules hold fibrils together
Gap is offset by a quarter of their length, hence “quarter stagger theory”
Types of Collagen
Type I
Strength
Most common type
Dermis, tendon, organ capsules, bone, dentin
Type II
Resists pressure
Hyaline and elastic cartilage
Type III
Delicate support meshwork
Lymphatic system, spleen, liver, lung, cardiovascular system
Make reticular fibers
Type IV
Attachment, filtration
Basal lamina
Collagen Formation
Transcription in nucleus
Translation to form alpha chains in Rough ER
Hydroxylate and glycosylated in Rough ER
Formation of procollagen in Rough ER
Has a tag at the end of them to prevent procollagen from self-aggregating inside the cell
Packaged and secreted via golgi through merocrine secretion
Cleavage to form tropocollagen by procollagen peptidase
Tropocollagen self-aggregates and lines up quarter-staggared to form fibrils
Self-assembly to form collagen fiber via lysyl oxidase
Defects in Collagen Formation
Scurvy
Vitamin C needed to hydroxylate proline
No hydroxylation means no hydrogen bonds and instabilitly
Collagen literally melts in body temperature
Capillary collagen collapse and cause little bleeds
Teeth held in sockets by ligaments; collapse of collagen and teeth falls out
Bruise very easily
Ehler-Danlos VII
Mutation in procollagen peptidase
No cleavage to form tropocollagen
Weaken stability
Tend to dislocate very easily and be super-flexible
Collagen wasting disease
Mutations in collagenase increase collagen turn over rate
High amounts of glycine in urine
Normally, collagen is turned over at a certain rate and needs to be replaced
Reticular Fibers
Branched network
Diagnostic: intersect at right angles
Argyophilic – silver loving
Taken up by polysaccharides
For delicate support
Contains lots of wandering cells
Needs space for wandering cell but support to keep spaces open
EM level shows that each fiber contains bundles of type III collagen fibrils surrounded by a sugar coat
Cross striations visible from type III collagen fibrils
Located in areolar connective tissue, liver, reticular, lymphatic and hemopoietic tissue
Ehlers-Danlos Type IV
Deficiency in Type III Collagen
Apparent in aorta which form aneurisms with form easily
Elastic fibers
Continuous network of “Y” branching fibers
Intersect at acute angles
“Chicken-wire” networks
Function is to stretch, up to 150x its original shape, reversibly
Location: blood vessels, lungs (forcing air back out of alveoli)
Secreted like collagen – have trophoelastin and proelastin precursors, etc.
EM morphology:
Amorphous elastin
Desmosine
Isodesmosine
Microfibrils
Disease of Elastin fibers
Marfan’s Syndome
Microfibrils not produced
G.I. problems
Tendency to rupture aorta and other blood vessels
Emphysema
Elastin fibers are damaged and regrow incorrectly
No longer able to force air out of alveoli
Become barrel cavity
Amorphous Ground Substances
Whats left after you remove all cells and fibers
No visible structure
Proteoglycans
Slippery and viscous
Protein core with sulfated glycoaminocylcans (GAGs) attached
In 3-D, they look like a bottle brush
6 types of GAG’s with different GAG’s or protein core to get a different proteoglycan
Common Proteoglycans:
Free
Aggrecan – most common
In collagen, Aggrecan links to chondroitin sulfate to form aggregates
Perlecan – has heprin sulfate
Transmembrane
Syndecan – has heparin sulfate and chondroitin sulfate
Fibroglycan
GAGs
Hyaluronic Acid
Non-sulfated
Long Chain of repeated disaccharides
Will swell up and takes up all the space it can
Negatively charged and attracts cations like Ca2+ and Na+ which in turn pulls in water
Slippery and resilient gel-like consistency that can resists compression
Forms physical barrier – bacteria produce hyaluronidases to break down barriers
Inhibits cell adhesion and facilitate cell migration
Connective Tissues Part 1
Dr. Robert Crissman, Ph.D.
Table of Contents
Definition
Classification of Connective Tissues
Functions of Connective Tissue
Composition of All Connective Tissues
Fixed Cells
Fibrocytes
Mesenchymal Cell
Reticular cells
White adipocytes
Lipid Storage
Brown fat cells
Wandering cells
Marcophage
Mast Cell
Plasma cells
Extracellular Fibers
Collagen Fibers
Types of Collagen
Collagen Formation
Defects in Collagen Formation
Reticular Fibers
Elastic fibers
Disease of Elastin fibers
Amorphous Ground Substances
Proteoglycans
GAGs
Interstitial Fluid
Glycoproteins